US12123023B2ActiveUtilityA1

Methods for generating stem cell-derived β cells and methods of use thereof

79
Assignee: HARVARD COLLEGEPriority: Dec 18, 2014Filed: Oct 15, 2021Granted: Oct 22, 2024
Est. expiryDec 18, 2034(~8.4 yrs left)· nominal 20-yr term from priority
Inventors:Douglas A. MeltonMads Gurtler
G01N 33/507C12N 2501/16A61K 35/39C12N 2501/727C12N 5/0676C12N 5/0678
79
PatentIndex Score
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Cited by
459
References
17
Claims

Abstract

Disclosed herein are methods for generating SC-β cells, and isolated populations of SC-β cells for use in various applications, such as cell therapy.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A composition comprising a population of PDX1-positive, NKX6.1-negative cells, a rho-associated protein kinase (ROCK) inhibitor, and a TGF-beta superfamily member. 
     
     
       2. The composition of  claim 1 , wherein the ROCK inhibitor is selected from the group consisting of: fasudil hydrochloride, GSK269962, GSK 429286, Y-27632, and Thiazovivin. 
     
     
       3. The composition of  claim 1 , wherein the ROCK inhibitor has a concentration of between about 0.1 μM and about 110 μM in said composition. 
     
     
       4. The composition of  claim 1 , wherein the TGF-beta superfamily member is selected from the group consisting of: Nodal, Activin A, Activin B, bone morphogenic protein-2 (BMP2), and bone morphogenic protein-4 (BMP4). 
     
     
       5. The composition of  claim 1 , wherein the composition further comprises KGF. 
     
     
       6. The composition of  claim 1 , wherein the composition further comprises Sant-1. 
     
     
       7. The composition of  claim 1 , wherein the composition further comprises retinoic acid. 
     
     
       8. The composition of  claim 1 , wherein the composition further comprises Sant-1 and retinoic acid. 
     
     
       9. The composition of  claim 8 , wherein the composition further comprises KGF. 
     
     
       10. The composition of  claim 9 , wherein the ROCK inhibitor is thiazovivin. 
     
     
       11. The composition of  claim 10 , wherein the TGF-beta superfamily member is activin A. 
     
     
       12. The composition of  claim 9 , wherein the TGF-beta superfamily member is activin A. 
     
     
       13. The composition of  claim 8 , wherein the ROCK inhibitor is thiazovivin. 
     
     
       14. The composition of  claim 8 , wherein the TGF-beta superfamily member is activin A. 
     
     
       15. The composition of  claim 1 , wherein the ROCK inhibitor is thiazovivin. 
     
     
       16. The composition of  claim 1 , wherein the TGF-beta superfamily member is activin A. 
     
     
       17. The composition of  claim 1 , wherein said population of pancreatic progenitor cells are not genetically modified.

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